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The present study explored the risk factors associated with radiotherapy in seniors diagnosed with limited-stage small cell lung cancer (LS-SCLC) to construct and validate a prognostic nomogram. The study retrospectively included 137 elderly patients with LS-SCLC who previously received radiotherapy. Univariate and multivariate COX analyses were conducted to identify independent risk factors and determine optimal cut-off values. Kaplan-Meier survival curves and nomograms were constructed to predict survival. Calibration and receiver operating characteristic (ROC) curves were used to evaluate the accuracy and consistency of the nomogram. Illness rating scale-geriatric (CIRS-G) score, treatment strategy, lymphocyte-to-monocyte ratio (LMR), white blood cell-to-monocyte ratio (WMR), and prognostic nutritional index (PNI) were discovered to be independent prognostic factors. Based on the findings of our multivariate analysis, a risk nomogram was developed to assess patient prognosis. Internal bootstrap resampling was utilized to validate the model, and while the accuracy of the AUC curve at 1 year was modest at 0.657 (95% CI 0.458-0.856), good results were achieved in predicting 3- and 5 year survival with AUCs of 0.757 (95% CI 0.670-0.843) and 0.768 (95% CI 0.643-0.893), respectively. Calibration curves for 1-, 3-, and 5 year overall survival probabilities demonstrated good cocsistency between expected and actual outcomes. Patients with concurrent chemoradiotherapy, CIRS-G score > 5 points and low PNI, WMR and LMR correlated with poor prognosis. The nomogram model developed based on these factors demonstrated good predictive performance and provides a simple, accessible, and practical tool for clinicians to guide clinical decision-making and study design.

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BACKGROUND: Perioperative use of opioids has revealed significant adverse effects associated with poor postoperative outcomes. OBJECTIVE: To determine whether opioid-free anaesthesia based on thoracic paravertebral block (TPVB) could improve postoperative recovery after breast cancer surgery. DESIGN: A randomised controlled trial. SETTING: A tertiary teaching hospital. PATIENTS: Eighty adult women undergoing breast cancer surgery were enrolled. Key exclusion criteria included remote metastasis (but not to axillary lymph nodes of the surgical side), contraindication to interventions or drugs and a history of chronic pain or chronic opioid use. INTERVENTIONS: Eligible patients were randomised at a 1 : 1 ratio to receive either TPVB-based opioid-free anaesthesia (OFA group) or opioid-based anaesthesia (control group). MAIN OUTCOME MEASURES: The primary outcome was the global score of the 15-item Quality of Recovery (QoR-15) questionnaire at 24 h after surgery. Secondary outcomes included postoperative pain and health-related quality of life. RESULTS: The QoR-15 global score was 140.3 ±â€Š5.2 in the OFA group and 132.0 ±â€Š12.0 in the control group ( P  < 0.001). The percentage of patients with good recovery (QoR-15 global score ≥118) was 100% (40/40) in the OFA group and 82.5% (33/40) in the control group ( P  = 0.012). Improved QoR in the OFA group was also evident in sensitivity analysis that rated QoR as excellent for a score of 136 to 150, as good at 122 to 135, as moderate at 90 to 121 and as poor at 0 to 89. The OFA group had higher scores in the domains of physical comfort (45.7 ±â€Š3.0 versus 41.8 ±â€Š5.7, P  < 0.001) and physical independence (18.3 ±â€Š2.2 versus 16.3 ±â€Š4.5, P  = 0.014). The two groups did not differ in pain outcomes or health-related quality of life. CONCLUSION: TPVB-based opioid-free anaesthesia improved early postoperative quality of recovery without compromising pain control in patients undergoing breast cancer surgery. TRIAL REGISTRATION: Clinicaltrials.gov; Identifier: NCT04390698.

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BACKGROUND: Pain management after pelvic and sacral tumor surgery is challenging and requires a multidisciplinary and multimodal approach. Few data on postoperative pain trajectories have been reported after pelvic and sacral tumor surgery. The aim of this pilot study was to determine pain trajectories within the first 2 weeks after surgery and explore the impact on long-term pain outcomes. METHODS: Patients scheduled for pelvic and sacral tumor surgery were prospectively recruited. Worst/average pain scores were evaluated postoperatively using questions adapted from the Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) until pain resolution was reached or up to 6 months after surgery. Pain trajectories over the first 2 weeks were compared using the k-means clustering algorithm. Whether pain trajectories were associated with long-term pain resolution and opioid cessation was assessed using Cox regression analysis. RESULTS: A total of 59 patients were included. Two distinct groups of trajectories for worst and average pain scores over the first 2 weeks were generated. The median pain duration in the high vs low pain group was 120.0 (95% CI [25.0, 215.0]) days vs 60.0 (95% CI [38.6, 81.4]) days (log rank p = 0.037). The median time to opioid cessation in the high vs low pain group was 60.0 (95% CI [30.0, 90.0]) days vs 7.0 (95% CI [4.7, 9.3]) days (log rank p < 0.001). After adjusting for patient and surgical factors, the high pain group was independently associated with prolonged opioid cessation (hazard ratio [HR] 2.423, 95% CI [1.254, 4.681], p = 0.008) but not pain resolution (HR 1.557, 95% CI [0.748, 3.243], p = 0.237). CONCLUSIONS: Postoperative pain is a significant problem among patients undergoing pelvic and sacral tumor surgery. High pain trajectories during the first 2 weeks after surgery were associated with delayed opioid cessation. Research is needed to explore interventions targeting pain trajectories and long-term pain outcomes. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov ( NCT03926858 , 25/04/2019).

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Objective: The aim of this study was to test the hypothesis whether serum level of calpains could become a meaningful biomarker for diagnosis of acute lung injury (ALI) in clinical after cardiac surgery using cardiopulmonary bypass (CPB) technology. Methods and results: Seventy consecutive adults underwent cardiac surgery with CPB were included in this prospective study. Based on the American-European Consensus Criteria (AECC), these patients were divided into ALI (n = 20, 28.57%) and non-ALI (n = 50, 71.43%) groups. Serum level of calpains in terms of calpains' activity which was expressed as relative fluorescence unit (RFU) per microliter and measured at beginning of CPB (baseline), 1 h during CPB, end of CPB as well as 1, 12, and 24 h after CPB. Difference of serum level of calpains between two groups first appeared at the end of CPB and remained different at subsequent test points. Univariate and multivariate logistic regression analysis indicated that serum level of calpains 1 h after CPB was an independent predictor for postoperative ALI (OR 1.011, 95% CI 1.001, 1.021, p = 0.033) and correlated with a lower PaO2/FiO2 ratio in the first 2 days (The first day: r = -0.389, p < 0.001 and the second day: r = -0.320, p = 0.007) as well as longer mechanical ventilation time (r = 0.440, p < 0.001), intensive care unit (ICU) length of stay (LOS) (r = 0.419, p < 0.001) and hospital LOS (r = 0.297, p = 0.013). Conclusion: Elevated serum level of calpains correlate with impaired lung function and poor clinical outcomes, indicating serum level of calpains could act as a potential biomarker for postoperative ALI following CPB in adults. Clinical trial registration: [https://clinicaltrials.gov/show/NCT05610475], identifier [NCT05610475].

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PURPOSE: To determine the effect of various cleaning methods for skin with acute radiation dermatitis (RD) in patients treated for nasopharyngeal carcinoma (NPC). METHODS: A total of 168 NPC inpatients were randomized, while 152 patients completed the whole trial and the data were analyzed. Patients were randomly divided into the non-washing group (Group 1), washing with water alone group (Group 2), and washing with water and soap group (Group 3). All three groups received intensity-modulated radiation therapy (IMRT) with other treatments. Follow-up from recruitment or the initial radiotherapy dose to 1 month after the final radiotherapy dose. CONSORT checklist was applied as the reporting guidelines for this study. The study evaluated a range of endpoints, including incidence, timing, severity of acute RD, and quality of life (QOL). RESULTS: There were no allergic reactions or aggravating in both washing groups during the whole treatment. The incidence of acute RD was 100% in all three groups, while the incidence of severe RD (grades 2-3) differed among groups (Group 1 vs. Group 2 vs. Group 3: 51% vs. 23.5% vs. 18%; P = 0.001), washing moderately reduced severity compared with patients without washing. Washing also delayed the onset time of acute RD; the incidence of acute RD was significantly lower than non-washing during the first 20 fractions (P < 0.001). What is more, washing reduced the incidence of moist desquamation (25.5% vs. 5.9% vs. 6%; P = 0.003) and helped relieve itching (6.49 ± 2.09 vs. 4.90 ± 1.90 vs. 4.00 ± 1.58; P < 0.001). There were no significant differences among groups with respect to pain or burning sensation. Washing improved QOL on physical (64.37 ± 4.08 vs. 67.41 ± 4.05 vs. 71.30 ± 4.87; P < 0.001), emotional (61.47 ± 4.75 vs. 65.75 ± 3.46 vs. 70.80 ± 3.27; P < 0.001), and social functional dimensions (62.64 ± 3.57 vs. 64.87 ± 3.88 vs. 68.04 ± 4.89; P < 0.001) at the end of radiotherapy, and the outcome was similar at 1 month after radiotherapy (P < 0.05). Washing with water and soap was the most effective way to reduce itching and improving QOL among the three groups (P < 0.05). CONCLUSION: Washing irradiated skin reduces the occurrence and severity of acute radiation dermatitis. CLINICAL TRIAL INFORMATION: ChiCTR2000038231, date of registration 09.18.2020.

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STUDY OBJECTIVE: Spinal fusion surgery is associated with severe postoperative pain. We examined whether bilateral ultrasound-guided erector spinae plane block could alleviate postoperative pain in patients undergoing lumbar spinal fusion. DESIGN: Blinded, randomized, controlled study. SETTING: Tertiary university hospital, operating room, postoperative recovery room and ward. PATIENTS: Sixty patients with American Society of Anesthesiologists grade I or II scheduled for lumbar spinal fusion surgery were randomized into the erector spinae plane block group (ESPB group) and the control group in a 1:1 ratio. INTERVENTIONS: Pre-operative ultrasound-guided bilateral erector spinae plane block was performed in the ESPB group, while sham subcutaneous infiltration was performed in the control group. MEASUREMENTS: The primary outcome was pain intensity at rest within 12 h postoperatively using the Numeric Rating Scale (NRS). Secondary outcomes included NRS pain scores at rest and on movement, postoperative opioid consumption and proportions of patients requiring opioid during the first 48 h after surgery. MAIN RESULTS: The ESPB group (n = 30) showed significantly lower pain scores at rest at 4 h after surgery (estimated mean difference - 1.6, 95% confidence interval [CI] -2.4 to -0.8, p < 0.001), at 8 h (-1.3, 95% CI -1.9 to -0.6, p < 0.001), and at 12 h (-0.7, 95% CI -1.3 to -0.1, p = 0.023). The two groups showed similar pain scores at rest at 24 h after surgery (estimated mean difference - 0.2, 95% CI -0.8 to 0.5) and 48 h (-0.3, 95% CI -0.8 to 0.2). The ESPB group also showed significantly lower pain score on movement at 4 h after surgery (-1.5, 95% CI -2.5 to -0.6). The ESPB group showed a significantly smaller proportion of patients requiring sufentanil within 12 h after surgery (p = 0.020), and the group consumed significantly less sufentanil during that period (p = 0.042). CONCLUSIONS: Bilateral ultrasound-guided erector spinae plane block improves postoperative analgesia in patients undergoing lumbar spinal fusion.

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This paper is to investigate the optimization conditions of ultrasonic technique for extraction process of Xiaoqinglong granules in medium scale. First of all, single factor experiment was used to determine the overall impact tendency and range of each factor； secondly, Box-Behnken method was used for optimization and detecting the content of paeoniflorin, ephedrine hydrochloride, glycyrrhizic acid of the liquid medicine. Their respective extraction rate was calculated and the comprehensive evaluation was carried out. The results were used as the evaluation basis for the efficacy of Xiaoqinglong granules ultrasonic extraction. The test results showed that the optimum extraction process of Xiaoqinglong granules by ultrasonic extraction was under the following conditions: ultrasonic power 600 W, liquid-solid ratio 10∶1, extraction for 31 min. Under this condition, the predicted value of extraction rate for Xiaoqinglong granules was 85.90%, and the test value was 85.87%. The mathematical model(P<0.01) established in this paper was significant, and can be used for the analysis and prediction of the ultrasonic extraction process of Xiaoqinglong granules.

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In order to understand at the tissue level how Aedes aegypti copes with toxic ammonia concentrations that result from the rapid metabolism of blood meal proteins, we investigated the incorporation of (15)N from (15)NH(4)Cl into amino acids using an in vitro tissue culture system. Fat body or midgut tissues from female mosquitoes were incubated in an Aedes saline solution supplemented with glucose and (15)NH(4)Cl for 10-40min. The media were then mixed with deuterium-labeled amino acids, dried and derivatized. The (15)N-labeled and unlabeled amino acids in each sample were quantified by mass spectrometry techniques. The results demonstrate that both tissues efficiently incorporate ammonia into amino acids, however, the specific metabolic pathways are distinct. In the fat body, the (15)N from (15)NH(4)Cl is first incorporated into the amide side chain of Gln and then into the amino group of Gln, Glu, Ala and Pro. This process mainly occurs via the glutamine synthetase (GS) and glutamate synthase (GltS) pathway. In contrast, (15)N in midgut is first incorporated into the amino group of Glu and Ala, and then into the amide side chain of Gln. Interestingly, our data show that the GS/GltS pathway is not functional in the midgut. Instead, midgut cells detoxify ammonia by glutamate dehydrogenase, alanine aminotransferase and GS. These data provide new insights into ammonia metabolism in A. aegypti mosquitoes.

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Mineralocorticoid receptor (MR) blockers attenuate cardiac remodeling in experimental models of heart failure, myocardial infarction and pressure-overload, in which the renin-angiotensin-aldosterone system is activated. Mice lacking the gene encoding guanylyl cyclase-A (GC-A), a common receptor for atrial and brain natriuretic peptide (ANP and BNP, respectively), show marked cardiac hypertrophy and fibrosis, which are almost completely inhibited by both genetic and pharmacological blockade of type 1 angiotensin II receptors. However, the effect of eplerenone, a specific MR blocker, on cardiac remodeling in GC-A knockout (GC-A KO) mice remains unknown. Male 12-week-old GC-A KO mice were assigned to control, eplerenone and hydralazine groups (n=6-7/group). Treatment with eplerenone at a dose of 100 mg/kg body weight/d reduced heart weight/body weight ratios, interstitial fibrosis and blood pressure to levels similar to those seen in wild type mice, in association with reduced transcription of atrial natriuretic peptide, brain natriuretic peptide, transforming growth factor-beta1, collagen I and collagen III. Although hydralazine (5 mg/kg body weight/d) exerted a similar effect on blood pressure, it did not inhibit the cardiac remodeling in GC-A KO mice. In conclusion, eplerenone attenuates cardiac remodeling in GC-A KO mice, most likely in a blood pressure-independent manner, which suggests that signaling downstream of MR is involved in the ventricular remodeling of GC-A KO mice.

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We have established a protocol to study the kinetics of incorporation of 15N into glutamine (Gln), glutamic acid (Glu), alanine (Ala) and proline (Pro) in Aedes aegypti females. Mosquitoes were fed 3% sucrose solutions containing either 80 mM 15NH4Cl or 80 mM glutamine labeled with 15N in either the amide nitrogen or in both amide and amine nitrogens. In some experiments, specific inhibitors of glutamine synthetase or glutamate synthase were added to the feeding solutions. At different times post feeding, which varied between 0 and 96 h, the mosquitoes were immersed in liquid nitrogen and then processed. These samples plus deuterium labeled internal standards were derivatized as dimethylformamidine isobutyl esters or isobutyl esters. The quantification of 15N-labeled and unlabeled amino acids was performed by using mass spectrometry techniques. The results indicated that the rate of incorporation of 15N into amino acids was rapid and that the label first appeared in the amide side chain of Gln and then in the amino group of Gln, Glu, Ala and Pro. The addition of inhibitors of key enzymes related to the ammonia metabolism confirmed that mosquitoes efficiently metabolize ammonia through a metabolic route that mainly involves glutamine synthetase (GS) and glutamate synthase (GltS). Moreover, a complete deduced amino acid sequence for GltS of Ae. aegypti was determined. The sequence analysis revealed that mosquito glutamate synthase belongs to the category of NADH-dependent GltS.

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A fragmentation mechanism for the neutral loss of 73 Da from dimethylformamidine glutamine isobutyl ester is investigated. Understanding this mechanism will allow to improve the identification and quantification of 15N-labeled and unlabeled glutamine and the distinguishing of glutamine and glutamic acid by electrospray ionization (ESI)-tandem mass spectrometry. Before mass spectrometry analysis, glutamine and glutamic acid are derivatized with dimethylformamide dimethyl acetal and isobutanol to form dimethylformamidine isobutyl ester. Derivatization conditions are modified based on an existing method to ensure complete derivatization of glutamic acid and to prevent the hydrolysis of glutamine. The fragmentation mechanism of dimethylformamidine glutamine isobutyl ester is studied and possible fragmentation pathways are proposed. Based on the fragmentation mechanism, a quantification method is developed to quantify both 15N-labeled and unlabeled glutamine and glutamic acid at a series of different neutral losses by performing multiple-reaction monitoring (MRM) scans in a triple-quadrupole mass spectrometer. Labeled glutamine includes 15N-amide labeled, 15N-amine labeled glutamine and glutamine 15N-labeled at both amide and amine positions. Deuterium labeled glutamine and glutamic acid are used as internal standards. Isotope effects are characterized for 15N labeled and deuterium labeled glutamine. It is found that the same method can be used to distinguish aspartic acid from asparagine. This study will improve the application of MS/MS for amino acid quantification and stable isotope labeling metabolism studies.

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This tutorial article introduces mass spectrometry (MS) for peptide fragmentation and protein identification. The current approaches being used for protein identification include top-down and bottom-up sequencing. Top-down sequencing, a relatively new approach that involves fragmenting intact proteins directly, is briefly introduced. Bottom-up sequencing, a traditional approach that fragments peptides in the gas phase after protein digestion, is discussed in more detail. The most widely used ion activation and dissociation process, gas-phase collision-activated dissociation (CAD), is discussed from a practical point of view. Infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD) are introduced as two alternative dissociation methods. For spectral interpretation, the common fragment ion types in peptide fragmentation and their structures are introduced; the influence of instrumental methods on the fragmentation pathways and final spectra are discussed. A discussion is also provided on the complications in sample preparation for MS analysis. The final section of this article provides a brief review of recent research efforts on different algorithmic approaches being developed to improve protein identification searches.

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